To determine how cell differentiation is stabilized and how it may be pathologically disturbed in the development of the craniofacial complex, the replication of chromatin in Chinese hamster ovary (CHO) cells and human fibroblasts will be studied. The aim is to learn how the clusters of protein that regulate gene expression in chromatin are faithfully copied. The basic premise to be tested is whether there exists a co-ordinated and complementary assembly of pre-existing and newly synthesized chromosomal proteins. The technique of Taichman and Freedlender (1975) will be used to determine (1) if any pre-existing proteins are permanently bound to the parental strand of DNA, (2) where the newly synthesized proteins assemble in replicating chromatin, and (3) how chromatin is repaired following "damage" to the DNA by a mutagen and a carcinogen. Preliminary results indicate that the nonhistone proteins may be permanently complexed with a unique strand of DNA. These results would suggest a new mechanism of action for some teratogens, a possible approach to the screening of teratogens, and would explain why embryonic cells and their progeny continue to malfunction following the initial insult. These results would also suggest how malignant transformation might arise and how the malignant property could be transmitted to the progeny cells.